Prostate cancer is the leading internal malignancy and the second most common cause of cancer deaths in American men. Current curative therapies for prostate cancer include surgery and external radiation therapy; however, both have significant morbidity and their impact on disease control has been less than complete, especially with radiotherapy. A novel approach to the control of cancer growth is gene therapy, a field that has progressed rapidly. Direct introduction of therapeutic genes into malignant cells in vivo may provide an effective treatment of solid tumors, including tumors of the prostate. One system employs the herpes simplex virus thymidine kinase (HSV-tk) gene, which codes for an enzyme that phosphorylates the nucleoside analogue ganciclovir (GCV) into a phosphorylated intermediate that is incorporated into newly synthesized DNA and terminates further replication, leading to cell death. Since normal mammalian cells do not possess this enzyme, cytotoxicity depends on the successful introduction and expression of the HSV-tk gene, phosphorylation of ganciclovir, and synthesis of DNA. Using both human and animal models for prostate cancer, we have demonstrated that adenovirus-mediated transfer of the HSV-tk gene and GCV treatment resulted in ablation of the tumors.